Three-dimensional biological scaffold compromising polymer waveguides

ABSTRACT

A three-dimensional biological scaffold. The scaffold includes at least three sets of polymer waveguides extending along at least three respective directions. The at least three sets of polymer waveguides interpenetrate each other at a plurality of nodes to form a self-supporting structure. In some embodiments, the polymer waveguides may be bio-degradable. In still some embodiments, the three-dimensional biological scaffold may include one or more coating layers for covering surfaces of the polymer waveguides.

CROSS-REFERENCE TO RELATED APPLICATION

This application relates to U.S. patent application Ser. No. 11/580,335,filed on Oct. 13, 2006, now U.S. Pat. No. 7,382,959, entitled “OpticallyOriented Three-Dimensional Polymer Microstructures,” the entire contentof which is incorporated herein by reference.

BACKGROUND OF THE INVENTION

The present invention relates to micro-structures. In particular, thepresent invention relates to biologically compatible micro-structuresand method of making the same.

Scaffold-based biological tissue engineering requires the formation ofnew tissues which is strongly dependent on the three-dimensional (3D)environment provided by the scaffold. Characteristics of the scaffoldthat can influence the 3D environment includes its composition, itsporous architecture, and its biological response to surroundingtissues/cellular media.

U.S. Pat. No. 6,379,962 (hereinafter the '962 patent) discloses apolymer scaffold having an extensively interconnected macroporousnetwork with macropores having microporous struts as walls. The polymermay be a bio-compatible or bio-degradable polymer. The polymer scaffoldis prepared by mixing a liquid polymer with particles, precipitating theliquid polymer with a non-solvent for the liquid polymer and dissolvingthe particles with a solvent to form the macroporous polymer scaffold.The surface of the polymer scaffold may be modified by acid or basetreatment, or by collagen or calcium phosphate deposition. However, thispolymer as disclosed in the '962 patent requires surface modificationwith acid or base treatment or by collagen or calcium phosphatedeposition. Furthermore, the structure of the polymer is foam-like withdisordered pores that are not homogeneous.

U.S. Pat. No. 6,875,442 (hereinafter the '442 patent) discloses apolymer scaffold with an interconnected macroporous network. The polymerscaffold disclosed embodies macropores having a diameter in a range of0.5-3.5 mm. The polymer scaffold is prepared using a process whichcombines the techniques of particulate leaching and phase inversion torender a process that provides amplified means by which to control themorphology of the resulting polymer scaffold. However, the structuredisclosed by the '442 patent is foam-like with disordered pores that arenot homogeneous.

Similar to the '442 patent, U.S. Pat. No. 7,022,522 (hereinafter the'522 patent) discloses a polymer scaffold that includes aninterconnected macroporous network. However, the polymer as disclosed inthe '522 patent requires multiple steps to manufacture includingparticulate leaching and phase inversion. Furthermore, the structure isfoam-like with disordered pores that are not homogeneous.

U.S. Pat. No. 6,993,406 (hereinafter the '406 patent) discloses a methodfor forming a three-dimensional biocompatible porous scaffold structureusing a solid freeform fabrication technique that can be used as amedical implant into a living organism. Imaging technology and analysisis first used to determine the three-dimensional design required for themedical implant, such as a bone implant or graft, fashioned as athree-dimensional, biocompatible scaffold structure. The technique isused to either directly produce the three-dimensional porous scaffoldstructure or to produce an over-sized three-dimensional porous scaffoldlattice which can be machined to produce the designed three-dimensionalporous scaffold structure for implantation. The method disclosed by the'406 patent, however, requires pre-fabrication software and canmanufacture bio-compatible ceramics only.

Therefore, it is desirable to provide an ordered 3D biological scaffoldthat can be manufactured in simple steps with ordered interconnectedpores with controlled pore size. Furthermore, it is desirable to have anordered 3D biological scaffold that can enable specific cell/tissuegrowth.

SUMMARY OF THE INVENTION

In accordance with the embodiments of the present invention, differentembodiments of a three-dimensional biological scaffold and a method ofmaking the same are provided.

In one embodiment according to the present invention, athree-dimensional (3D) biological scaffold is provided. The 3Dbiological scaffold includes at least three sets of bio-degradablepolymer waveguides extending along at least three respective directions.The at least three sets of bio-degradable polymer waveguidesinterpenetrate each other at a plurality of nodes to form aself-supporting structure having a plurality of ordered interconnectedpores. The plurality of ordered interconnected pores are sized tofacilitate ingress of at least one of biological cells, vascular tissue,or nutrient media.

The plurality of ordered interconnected pores may can sized to about100-300 μm for trabecular bone implants. A bio-degradable polymerwaveguide of the at least three sets of bio-degradable polymerwaveguides may have a cross-sectional diameter about 1 μm to about 1 mm.The plurality of ordered interconnected pores may occupy a free space ofnot less than about 40% by volume and not greater than about 99% byvolume of the self-supporting structure. The at least three sets ofbio-degradable polymer waveguides may include a bio-degradable polymerselected from one of starches, starch-similar polymers, starch-syntheticblend polymers, esters, amides, anhydrides, urethanes, ureas,carbonates, or saccharides. Surfaces of the three-dimensional biologicalscaffold may be treated to facilitate cellular recognition andproliferation with a material that has affinity for one of polymeric,ceramic, or metallic surfaces. The material may include one of a silane,a bi-phasic calcium phosphate, a bone morphogenetic protein, apolysaccharide, a biochemical agent, or a mineral precursor.

In another embodiment, a three-dimensional biological scaffold isprovided. The three-dimensional biological scaffold includes at leastthree sets of polymer waveguides extending along at least threerespective directions. Surfaces of the at least three sets of polymerwaveguides are coated with one or more coating layers. The at leastthree sets of polymer waveguides interpenetrate each other at aplurality of nodes to form a self-supporting structure having aplurality of ordered interconnected pores. The plurality of orderedinterconnected pores are sized to facilitate ingress of at least one ofbiological cells, vascular tissue, or nutrient media.

The plurality of ordered interconnected pores may be sized to about 250μm. The one or more coating layers may include one of metal or ceramic.The one or more coating layers may include a material selected from oneof titanium (Ti), nickel (Ni), Ti6Al4V, or nickel alloy. The one or morecoating layers may include a material selected from one of siliconcarbide (SiC), silicon nitride (Si3N4), hafnium carbide (HfC), chromiumcarbide (Cr3C2), boron nitride (B4N), 1:5 cubic boron nitride (c-BN),hexagonal boron nitride (h-BN), boron carbide (B4C), aluminum oxide(Al2O3), titanium diboride (TiB2), titanium nitride (TiN), or zirconiumdioxide (ZrO2). A polymer waveguide of the at least three sets ofpolymer waveguides may have a cross-sectional diameter from about 1 μmto about 1 mm. The polymer waveguide may have a cross-sectional diameterfrom about 100 μm to about 500 μm. The plurality of orderedinterconnected pores may occupy a free space of not less than about 40%by volume and not greater than about 99% by volume of theself-supporting structure. The free space may be not less than about 70%by volume and not greater than about 90% by volume of theself-supporting structure. Surfaces of the three-dimensional biologicalscaffold may be treated to facilitate cellular recognition andproliferation with a material that has affinity for one of polymeric,ceramic, or metallic surfaces. The material may include one of a silane,a bi-phasic calcium phosphate, a bone morphogenetic protein, apolysaccharide, a biochemical agent, or a mineral precursor.

In still another embodiment, a method for forming a three-dimensionalbiological scaffold is provided. A volume of photo-monomer is secured. Amask having a plurality of apertures is placed between at least onecollimated light source and the volume of photo-monomer. A plurality ofcollimated light beams from the at least one collimated light source isdirected through the plurality of apertures into a portion of the volumeof photo-monomer to polymerize the portion to form a plurality ofbio-degradable polymer waveguides. And, photo-monomer of the volume ofphoto-monomer not polymerized is removed to leave behind thethree-dimensional biological scaffold having a plurality of orderedinterconnected pores. At least three of the plurality of bio-degradablepolymer waveguides intersect each other at an aperture of the pluralityof apertures. The quantity and opening sizes of the plurality ofapertures are selected to adjust the quantity and dimensions of theplurality of ordered interconnected pores to facilitate ingress of atleast one of biological cells, vascular tissue, or nutrient media. Theplurality of ordered interconnected pores may occupy a free space of notless than about 40% by volume and not greater than about 99% by volumeof the three-dimensional biological scaffold.

In yet another embodiment, a method for forming a three-dimensionalbiological scaffold is provided. A volume of photo-monomer is secured. Amask having a plurality of apertures is placed between at least onecollimated light source and the volume of photo-monomer. A plurality ofcollimated light beams from the at least one collimated light source isdirected through the plurality of apertures into a portion of the volumeof photo-monomer to polymerize the portion to form a plurality ofpolymer waveguides. Photo-monomer of the volume of photo-monomer notpolymerized is removed to leave behind the three-dimensional biologicalscaffold having a plurality of ordered interconnected pores. And,surfaces of the plurality of polymer waveguides are covered with one ormore coating layers. At least three of the plurality of polymerwaveguides intersect each other at an aperture of the plurality ofapertures. The quantity and opening sizes of the plurality of aperturesare selected to adjust the quantity and dimensions of the plurality ofordered interconnected pores to facilitate ingress of at least one ofbiological cells, vascular tissue, or nutrient media.

The plurality of ordered interconnected pores may occupy a free space ofnot less than about 40% by volume and not greater than about 99% byvolume of the three-dimensional biological scaffold. The one or morecoating layers may include metal, and the one or more coating layers mayinclude ceramic.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a system to form a single waveguidefrom a single collimated beam through a single aperture pursuant toaspects of the present invention.

FIG. 2 is a schematic diagram of a system to form multiple waveguidesfrom a single collimated beam or multiple collimated beams through asingle aperture pursuant to aspects of the present invention.

FIG. 3 is a schematic diagram of a system to form a 3D structure (e.g.,a 3D ordered polymer microstructure) formed from multiple waveguidescreated using a single collimated beam or multiple collimated beamsthrough multiple apertures pursuant to aspects of the present invention.

FIG. 4 a illustrates an example of a square mask pattern (or a squaremask aperture pattern) pursuant to aspects of the present invention.

FIG. 4 b illustrates an example of a hexagonal mask pattern (or ahexagonal mask aperture pattern) pursuant to aspects of the presentinvention.

FIG. 5 illustrates an example of a 3D polymer scaffold pursuant toaspects of the present invention.

FIG. 6 illustrates a cross-sectional view of another example of a 3Dpolymer scaffold pursuant to aspects of the present invention.

DETAILED DESCRIPTION

The present invention will now be described more fully hereinafter withreference to the accompanying drawings, in which exemplary embodimentsof the invention are shown. The dimensions of layers and other elementsshown in the accompanying drawings may be exaggerated to more clearlyshow details. The present invention should not be construed as beinglimited to the dimensional relations shown in the drawings, nor shouldthe individual elements shown in the drawings be construed to be limitedto the dimensions shown.

Embodiments of the present invention provide a 3D biological scaffold,defined by a microtruss structure made of a polymeric, ceramic ormetallic material, that has application in biological systems. The 3Dbiological scaffold may be made solely of a polymer (e.g.,bio-degradable or other), ceramic, metal, or any combination thereofwith the microtruss structure. An optically templated polymer scaffolddetermines the final shape and dimensions of the 3D biological scaffoldwhich has the proper pore size and surface chemistry to provides anoptimal environment for vascular, cellular, and biomineralgrowth/remodeling.

An ideal 3D biological scaffold should have appropriate mechanicalproperties, adequate degradation rate, porosity, interconnectivity, andpermeability to allow ingress of cells, vascular tissue, and othernutrient media. The diameter of the pores of the 3D biological scaffoldshould be at least 100 micron and not larger than 300 micron to enablecell penetration into the structure, to allow tissue ingrowths and toallow blood supply and nutrient to get into the scaffold. For example,the pore size of the 3D biological scaffold may be sized to 250 micronto facilitate trabecular bone implant application. In addition, havingthe proper surface chemistry is required to enhance cell recognition,attachment, and proliferation. A simple polymerization scheme allows fora controllable, reproducible polymeric structure having a 3D porousnetwork with controlled porosity and surface chemistry. Unlike otherknown scaffolds in the art, which lack an interconnected porous network,embodiments of the present invention provide an ordered 3D structurewith optimized characteristics, for example, pore scale andinterconnectivity, for a particular biological system based on celldiameter, chemistry and other factors.

The present invention has applications in many areas. For example, themedical, dental, and orthopedic communities need biologically compatiblestructures that provide ideal templating, porosity and interconnectivityfor cell, bone, and tooth growth. Embodiments of the present inventioncan enable polymeric, ceramic, and metallic structures that are ideal orhighly compatible for tissue engineering.

Embodiments of the present invention are based on a 3D polymer scaffold.The techniques of making the 3D polymer scaffold are disclosed in arelated U.S. patent application Ser. No. 11/580,335 (hereinafter the'335 application) entitled “Optically Oriented Three-Dimensional PolymerMicrostructures,” which is incorporated herein by reference in itsentirety. The '335 application discloses a method and system offabricating porous cellular polymer materials with an ordered 3Dmicrostructure using a simple technique. These cellular materials arecreated from a pattern of self-propagating polymer waveguides, which areformed in an appropriate photopolymer. More detail of the techniques canbe found in the '335 application.

In reference to the '335 application, a fixed light input (e.g.,collimated UV light) is used to cure (i.e., polymerize) polymer opticalwaveguides, which can self-propagate in a 3D pattern. The propagatedpolymer optical waveguides form an ordered 3D microstructure that can bepolymerized without anything moving during the formation process toprovide a path to large scale, inexpensive production.

Some liquid polymers, referred to as photopolymers, undergo a refractiveindex change during the polymerization process. The refractive indexchange can lead to a formation of polymer optical waveguides. If amonomer that is photo-sensitive is exposed to light (e.g., typically UV)under the right conditions, the initial area of polymerization, such asa small circular area, will “trap” the light and guide it to the tip ofthe polymerized region, further advancing that polymerized region. Thisprocess will continue, leading to the formation of a waveguide structurewith approximately the same cross-sectional dimensions along its entirelength.

The '335 application discloses a polymer cellular material with anordered 3D microstructure by creating a pattern of self-propagatingoptical waveguides in an appropriate photopolymer. A formation of asingle and multiple polymer waveguides will be described in more detailbelow, followed by a more detailed description on how to pattern thesepolymer waveguides to form an ordered 3D microstructure.

Formation of a Single Polymer Waveguide with Single Aperture

Referring to FIG. 1, a system to form a single optical waveguideincludes a collimated light source 100, a reservoir 110 (e.g., a mold)having a volume of monomer 120 that will polymerize at a wavelength of acollimated light beam 170 provided by the light source 100, and apatterning apparatus, such as a mask 130 with a single aperture 140(e.g., an open area) of a given shape and dimension.

The single collimated beam 170 is directed through the aperture 140 inthe mask 130 to the monomer 120. Between the mask 130 and the monomer120, there may be a substrate 150. The substrate can be composed of amaterial, such as glass, Mylar, and other suitable materials that willtransmit the incident light beam to the monomer 120. That is, in oneembodiment of the present invention, the substrate 150 is substantiallytransparent to the incident light beam. On the surface of the monomer120, in the area exposed to a portion of the light beam, an opticalwaveguide 160 will begin to polymerize.

The index of refraction change between the polymer and monomer will“trap” and “focus” the light in the polymer and guide the polymerizationprocess. Due to this self-guiding/self-focusing effect, the polymerizedwaveguide 160 will form with an approximately constant cross-section anda length much greater than the cross-sectional dimensions. The directionin which this polymer waveguide 160 will grow is dependent on thedirection of the incident beam. The cross-section of the polymerwaveguide 160 is dependent on the shape and dimensions of the incidentcollimated beam, which in turn is dependent on the shape and dimensionsof the aperture 140 in the mask 130. The length to which the polymerwaveguide 160 can “grow” is dependent on a number of parametersincluding the size, intensity, and exposure time of the incident beam,as well as the light absorption/transmission properties of thephotopolymer. The time in which it takes to form a polymer waveguidedepends on the kinetics of the polymerization process.

To put it another way, when the portion of the collimated light beampasses through the mask 130 and first hits the liquid photo-monomer 120,a polymer “tip” is formed. There is a large enough difference betweenthe refractive index of the monomer and the polymer to cause internalreflection of the light in the polymer—this is the same principle aswhen light travels through fiber optics. Because of this internalreflection effect, the light is essentially focused to the tip of thepolymer, causing the monomer at the tip to cure (i.e., polymerize). Thiswill also propagate the tip of the polymer through the liquid monomer120, forming the self-propagating polymer optical waveguide 160. Inaddition, because of this internal reflection affect, the waveguide 160can be “very” long with respect to the cross-sectional dimensions, allwhile maintaining a constant cross-section through its length.Eventually the formation of the polymer waveguide 160 will stop at theend of the monomer reservoir 110, or it will stop prior to that if thereis not enough energy to polymerize the monomer 120. This happens becausethe polymer itself will absorb some of the portion of the collimatedlight beam passing through the mask 130.

Formation of Multiple Polymer Waveguides with Single Aperture

As mentioned above, the direction in which the polymer waveguide willform is dependent on the angle of the incident collimated beam. If thecollimated beam is perpendicular to a flat monomer surface (as shown inFIG. 1), the polymer waveguide will propagate, or grow perpendicular tothe monomer surface. By contrast, referring to FIG. 2, if the incidentcollimated beam is directed at an angle, the polymer waveguide will growat an angle relative to the monomer surface. Note this angle will beaffected by the change in refractive index between the air and/orsubstrate and the monomer due to refraction.

That is, as shown in FIG. 2, a system to form multiple opticalwaveguides 260 includes one or more collimated light sources 200, areservoir 210 (e.g., mold) having a volume of monomer 220 that willpolymerize at a wavelength of collimated light beams provided by thelight sources 200, and a patterning apparatus, such as a mask 230 with asingle aperture (e.g., open area) 240 of a given shape and dimension.Between the mask 230 and the monomer 220, there may be a substrate 250.

Through the single aperture 240 as described above, the multiplewaveguides 260 can be formed by directing multiple collimated beams atdifferent angles through the aperture 240. That is, in one embodiment ofthe invention, a single collimated light source is used. Multiplewaveguides are formed from a plurality of exposures of the collimatedlight beam of the single collimated light source with a mask having asingle aperture, and the single collimated light source is adapted tomove with respect to the mask between each of the exposures.

Alternatively, the multiple waveguides 260 can be formed one at a timethrough the single aperture 240 by simply changing the incident angle ofa single collimated beam after the formation of each of the waveguides240. That is, in another embodiment of the present invention, multiplecollimated light sources are adapted to produce and direct multiplecollimated light beams at different angles with respect to a point of amask having a single aperture. Multiple waveguides are formed from asingle exposure of the multiple light beams of the multiple collimatedlight sources with the mask having the single aperture.

Formation of 3D Microstructure Using Patterned Optical Waveguides

The technique to create a 3D polymer microstructure is based on theabove described approach for forming multiple optical waveguides with asingle aperture. However, instead of using a mask with a singleaperture, a mask with a two-dimensional pattern of apertures is used tocreate a three-dimensional polymer microstructure as is shown in FIG. 3.

Referring to FIG. 3, a system to form a 3D polymer microstructureincludes one or more collimated light sources 300, a reservoir (e.g., amold) 310 having a volume of monomer 320 that will polymerize at awavelength of collimated light beams provided by the light sources 300,and a patterning apparatus, such as a mask 330 with multiple apertures(e.g., open areas) 340. Each of the apertures 340 has a given shape anddimension substantially matching a cross section geometry of a polymerwaveguide 360. Between the mask 330 and the monomer 320, there may be asubstrate 350. Here, in FIG. 3, a truly 3D network can be formed becausethe intersecting polymer waveguides 360 will simply polymerize together,but will not interfere with waveguide propagation. Also, the spacingbetween the plurality of waveguides 360 corresponds with the pattern ofthe plurality of apertures 340. The pattern of the apertures 340 may,for example, be in a square pattern as shown in FIG. 4 a and/or in ahexagonal pattern as shown in FIG. 4 b. The hole (i.e., aperture)spacing, i.e., distance between apertures 340 in the mask 330, and thenumber of waveguides 360 formed from each of the apertures 340 willdetermine the open volume fraction (i.e., open space) of the formed 3Dmicrostructure. It should be appreciated by a person skilled in the artthat once a certain pore size is determined for a particularapplication, the hole spacing and the size of the aperture can beadjusted accordingly to produce the desired pore size.

As such, through the process shown in FIG. 3, an exemplary 3D polymerscaffold 500 (e.g., a 3D ordered polymer microstructure) can be designedand provided as shown in FIG. 5. The design parameters include: 1) theangle and pattern of the polymer waveguides with respect to one another;2) the packing, or relative density of the resulting cellular structure(or the open volume fraction); and 3) the cross-sectional shape anddimensions of the polymer waveguides. By varying these designparameters, the exemplary 3D polymer scaffold 500 can be adapted tofacilitate a particular implant application. By way of example, in humantrabecular bone implant application, the pore size of the scaffold canbe within the range of 0.5 to 3.5 mm to match the pore size of humantrabecular bone. The high level of interconnectivity of the pores of the3D polymer scaffold 500 enhances both penetration of the scaffold 500 bycells and nutrient flow to the cells.

In one embodiment according to the present invention, the 3D polymerscaffold 500 includes bio-degradable polymer such as, but not limitedto, starches, starch-similar polymers, starch-synthetic blend polymers,esters, amides, anhydrides, urethanes, ureas, carbonates, orsaccharides.

In another embodiment according to the present invention, the trusselements (i.e., the waveguides 360) may have diameters between about 1μm and about 1 mm, and the 3D polymer scaffold can has between 40% and99% of interconnected free space.

In still another embodiment according to the present invention, the 3Dpolymer scaffold 602 can be deposited with one or more layers ofmaterial 604 as shown in FIG. 6. The layers of material can be, but notlimited to, ceramic or metal. Exemplary ceramic can be, but not limitedto, one of silicon carbide (SiC), silicon nitride (Si3N4), hafniumcarbide (HfC), chromium carbide (Cr3C2), boron nitride (B4N), cubicboron nitride (c-BN), hexagonal boron nitride (h-BN), boron carbide(B4C), aluminum oxide (Al2O3), titanium diboride (TiB2), titaniumnitride (TiN), or zirconium dioxide (ZrO2). Exemplary metal can be, butnot limited to, one of titanium (Ti), nickel (Ni), Ti6Al4V, or nickelalloy. The layers of material can be applied by chemical vapordeposition, reacting the 3D polymer scaffold with a gas or liquid phasereactant, or coating the 3D polymer scaffold with a suitable pre-ceramicpolymer.

In yet another embodiment according to the present invention, the 3Dpolymer scaffold's surface is treated to enable specificfunctionalities, such as specific cellular recognition and proliferationneeded to stimulate cell growth and achieve bio-compatibility. Byimmersing a ceramic or metal coated 3D polymer scaffold in a solutionbath of various mono- or multi-functional molecules (e.g., biochemicalagents or mineral precursor), a biologically specific surface can beproduced. The functional molecules can have an affinity for polymeric,ceramic, or metallic surfaces. This treated 3D polymer scaffold canprovide bone-implant scaffolds absorption/recognition sites formolecular/cellular species such as bone morphogenetic proteins andbi-phasic calcium phosphate that are critical to osteogenesis. Thesemolecules/minerals are critical during osteoinduction (i.e., allows forcell differentiation and bone morphogenesis). In addition, pore size andsurface functionality are critical during osteogenesis (i.e., formingbone), whereby proper adsorption sites and transportation pathways areprovided by the 3D scaffold to the bone-mineralizing cells (i.e.,osteoblasts). Cell transport is also critical during remodeling of bone;that is, it is necessary to transport bone-resorbing cells (i.e.,osteoclasts) to growing/remodeled bone.

Although certain exemplary embodiments of the present invention havebeen disclosed for illustrative purposes, those skilled in the art wouldappreciate that various modifications, additions and subtractions arepossible, without departing from the scope and spirit of the presentinvention as disclosed in the accompanying claims and their equivalents.

1. A three-dimensional biological scaffold comprising: at least threesets of bio-degradable polymer waveguides extending along at least threedifferent directions, wherein the at least three sets of bio-degradablepolymer waveguides interpenetrate each other at a plurality of nodes toform a self-supporting structure having a plurality of orderedinterconnected pores, at least three of the bio-degradable polymerwaveguides intersecting each other at a node of the plurality of nodesat non-perpendicular angles, and wherein the plurality of orderedinterconnected pores are sized to facilitate ingress of at least one ofbiological cells, vascular tissue, or nutrient media.
 2. Thethree-dimensional biological scaffold of claim 1, wherein the pluralityof ordered interconnected pores are sized to about 100 μm to 300 μm. 3.The three-dimensional biological scaffold of claim 1, wherein abio-degradable polymer waveguide of the at least three sets ofbio-degradable polymer waveguides has a cross-sectional diameter about 1μm to about 1 mm.
 4. The three-dimensional biological scaffold of claim1, wherein the plurality of ordered interconnected pores occupy a freespace of not less than about 40% by volume and not greater than about99% by volume of the self-supporting structure.
 5. The three-dimensionalbiological scaffold of claim 1, wherein the at least three sets ofbio-degradable polymer waveguides comprise a bio-degradable polymerselected from one of starches, starch-similar polymers, starch-syntheticblend polymers, esters, amides, anhydrides, urethanes, ureas,carbonates, or saccharides.
 6. The three-dimensional biological scaffoldof claim 1, wherein surfaces of the three-dimensional biologicalscaffold are treated with a material selected from the group consistingof a silane, a biphasic calcium phosphate, a bone morphogenetic protein,and a polysaccharide.
 7. A three-dimensional biological scaffoldcomprising: at least three sets of polymer waveguides extending along atleast three different directions; and one or more coating layers onsurfaces of the at least three sets of polymer waveguides, wherein theat least three sets of polymer waveguides interpenetrate each other at aplurality of nodes to form a self-supporting structure having aplurality of ordered interconnected pores, at least three of the polymerwaveguides intersecting each other at a node of the plurality of nodesat non-perpendicular angles, and wherein the plurality of orderedinterconnected pores are sized to facilitate ingress of at least one ofbiological cells, vascular tissue, or nutrient media.
 8. Thethree-dimensional biological scaffold of claim 7, wherein the pluralityof ordered interconnected pores are sized to about 100 μm to 300 μm. 9.The three-dimensional biological scaffold of claim 7, wherein the one ormore coating layers comprise one of metal or ceramic.
 10. Thethree-dimensional biological scaffold of claim 9, wherein the one ormore coating layers comprise a material selected from one of titanium(Ti), nickel (Ni), Ti6Al4V, or nickel alloy.
 11. The three-dimensionalbiological scaffold of claim 9, wherein the one or more coating layerscomprise a material selected from one of silicon carbide (SiC), siliconnitride (Si3N4), hafnium carbide (HfC), chromium carbide (Cr3C2), boronnitride (B4N), cubic boron nitride (c-BN), hexagonal boron nitride(h-BN), boron carbide (B4C), aluminum oxide (Al2O3), titanium diboride(TiB2), titanium nitride (TiN), or zirconium dioxide (ZrO2).
 12. Thethree-dimensional biological scaffold of claim 7, wherein a polymerwaveguide of the at least three sets of polymer waveguides has across-sectional diameter from about 1 μm to about 1 mm.
 13. Thethree-dimensional biological scaffold of claim 12, wherein the polymerwaveguide has a cross-sectional diameter from about 100 μm to about 500μm.
 14. The three-dimensional biological scaffold of claim 7, whereinthe plurality of ordered interconnected pores occupy a free space of notless than about 40% by volume and not greater than about 99% by volumeof the self-supporting structure.
 15. The three-dimensional biologicalscaffold of claim 14, wherein the free space is not less than about 70%by volume and not greater than about 90% by volume of theself-supporting structure.
 16. The three-dimensional biological scaffoldof claim 7, wherein surfaces of the three-dimensional biologicalscaffold are treated with a material selected from the group consistingof a silane, a bi-phasic calcium phosphate, a bone morphogeneticprotein, and a polysaccharide.